Objective:

Design of Libra study (NOE-TGN-201) in trigeminal neuralgia

Background:

Trigeminal neuralgia (TN) is a debilitating severe facial pain condition with high unmet need.

Evidence indicates that metabotropic glutamate receptors 5 (mGluR5) are involved in pain transmission and central pain processing.

Basimglurant is a highly selective mGluR5 NAM with high affinity and superior in vitro potency over other NAMs on intracellular mGluR5. An optimized modified release oral formulation demonstrated robust receptor occupancy, good bioavailability, and half-life allowing once daily (OD) dosing. In previous trials, basimglurant has been well tolerated.

LIBRA is an enriched randomized withdrawal trial assessing basimglurant in TN. The design accounts for the severe pain associated with TN and strong patient/researcher needs for access to potentially active treatment using a non-parallel placebo-controlled group design.

Design/Methods:

LIBRA is a Phase 2/3, international, multi-center study evaluating safety and efficacy of monotherapy basimglurant in adult patients with classical or idiopathic TN (NOE-TGN-201, NCT05217628). Patients with paroxysms only or with paroxysms and continuous pain (CP), with suboptimal response to current therapy, are enrolled. LIBRA starts with a 4W screening, followed by an 8W open label active run-in (P1) and a 12W, double blind, placebo-controlled, randomized withdrawal period (P2). In P1, Participants receive 1.5 to 3.5mg basimglurant OD. In P2, responders are randomized according to randomized withdrawal design. P2 completers are offered a 52W open label extension.

Results:

LIBRA aims to include 200 participants to randomize 70. In P1, response is: ≥30% improvement of paroxysm severity, frequency, CP severity if present or pain interference. P2 primary endpoint is time to loss of efficacy. Secondary endpoints include changes in paroxysms severity, CP severity, pain interference or Penn-FPS-R, PGI-C and MSQ scores. Safety and tolerability are assessed.

Conclusions:

The LIBRA trial will characterize the efficacy and safety profile of basimglurant, a novel mGluR5 NAM, in patients with TN.